ethyl {(1,3-benzothiazol-2-ylmethyl)[(2-bromo-4-methyl-1,3-thiazol-5-yl)carbonyl]amino}acetate | 1016645-44-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl {(1,3-benzothiazol-2-ylmethyl)[(2-bromo-4-methyl-1,3-thiazol-5-yl)carbonyl]amino}acetate
• 英文别名: Ethyl {(1,3-benzothiazol-2-ylmethyl)[(2-bromo-4-methyl-1,3-thiazol-5-yl)carbonyl]amino}acetate；ethyl 2-[1,3-benzothiazol-2-ylmethyl-(2-bromo-4-methyl-1,3-thiazole-5-carbonyl)amino]acetate
• CAS: 1016645-44-5
• 化学式: C₁₇H₁₆BrN₃O₃S₂
• 分子量: 454.368
• InChiKey: BBVKWKXTLALCDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  129
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-氨基-3-甲氧基苯硼酸频那醇酯 、 ethyl {(1,3-benzothiazol-2-ylmethyl)[(2-bromo-4-methyl-1,3-thiazol-5-yl)carbonyl]amino}acetate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 水 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 ((1,3-benzothiazol-2-ylmethyl){[2-(4-amino-3-methoxyphenyl)-4-methyl-1,3-thiazol-5-yl]carbonyl}amino)acetic acid
  参考文献：
  名称：

  Towards Gram-negative antivirulence drugs: New inhibitors of HldE kinase

  摘要：

  Gram-negative bacteria lacking heptoses in their lipopolysaccharide (LPS) display attenuated virulence and increased sensitivity to human serum and to some antibiotics. Thus inhibition of bacterial heptose synthesis represents an attractive target for the development of new antibacterial agents. HldE is a bifunctional enzyme involved in the synthesis of bacterial heptoses. Development of a biochemical assay suitable for high-throughput screening allowed the discovery of inhibitors 1 and 2 of HldE kinase. Study of the structure-activity relationship of this series of inhibitors led to highly potent compounds. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.021
• 作为产物：
  描述：

  2-溴-4-甲基噻唑-5-羧酸 、 ethyl [(1,3-benzothiazol-2-ylmethyl)amino]acetate 在 草酰溴 、 N,N-二甲基甲酰胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到ethyl {(1,3-benzothiazol-2-ylmethyl)[(2-bromo-4-methyl-1,3-thiazol-5-yl)carbonyl]amino}acetate
  参考文献：
  名称：

  Chemical inhibitors of bacterial heptose synthesis, methods for their preparation and biological applications of said inhibitors

  摘要：

  本发明涉及具有抑制庚糖合成特性的新化合物，其具有式(I)或其药学上可接受的盐或前药，其中A为芳基或杂环，任选地被一个或多个相同或不同的R取代，如H、C1-C10烷基、C1-C10烷基-OR1、C1-C10烷基-NR1R1、烷氧基、羟基、硫代烷基、芳基、杂环、卤素、硝基、氰基、CO2R1、NR1R1、NR1C(O)R1、C(O)NR1R1、NR1C(S)R1、C(S)NR1R1、SO2NR1R1、SO2R1、NR1SO2R1、NR1C(O)NR1R1、NR1C(O)OR1、NR1C(S)NR1R1、NR1C(S)OR1、R1C═NOR1、C(O)R1、芳氧基、硫代芳基、烯基、炔基，R1相同或不同为H或C1-C10烷基；B1、B2、B3相同或不同，代表C、N、O、S以形成五元芳香环，其中一到三个碳原子被选自S、O、N的杂原子替换，任选地被一个或多个相同或不同的如上定义的R取代；B4为C或N；Y为H、C1-C10烷基、烷氧基、硫代烷基，任选地被一个或多个相同或不同的如上定义的R取代；W为C、O或N，被或不被一个或多个C1-C10烷基基团取代；D为任选地被一个或多个相同或不同的如上定义的R取代的杂环。

  公开号：

  US20100022541A1

文献信息

• Chemical inhibitors of bacterial heptose synthesis, methods for their preparation and biological applications of said inhibitors
  申请人：Escaich Sonia

  公开号：US20100022541A1

  公开（公告）日：2010-01-28

  The invention relates to new compounds having heptose synthesis inhibitory properties, of formula (I) or a pharmaceutically acceptable salt, or prodrug thereof, wherein A is an aryl or heterocycle, optionally substituted by one or several identical or different R such as H, C1-C10 alkyl, C1-C10 alkyl-OR 1 , C1-C10 alkyl-NR 1 R 1 , alkoxy, hydroxy, thioalkyl, aryl, heterocycle, halogen, nitro, cyano, CO 2 R 1 , NR 1 R 1 , NR 1 C(O)R 1 , C(O)NR 1 R 1 , NR 1 C(S)R 1 , C(S)NR 1 R 1 , SO 2 NR 1 R 1 , SO 2 R 1 , NR 1 SO 2 R 1 , NR 1 C(O)NR 1 R 1 , NR 1 C(O)OR 1 , NR 1 C(S)NR 1 R 1 , NR 1 C(S)OR 1 , R 1 C═NOR 1 , C(O)R 1 , aryloxy, thioaryl, alkenyl, alkynyl R1 identical or different is H or C1-C10 alkyl B 1 , B 2 , B 3 identical or not represent C, N, O, S to form a five-membered aromatic ring wherein from one to three carbon atoms are replaced by a heteroatom selected from S, O, N optionally substituted by one or several identical or different R such as defined above B 4 is C or N Y is H, C1-C10 alkyl, alkoxy, thio-alkyl, optionally substituted by one or several identical or different R such as defined above W is C, O or N, substituted or not by one or several C1-C10 alkyl radicals D is an heterocycle optionally substituted by one or several identical or different R such as defined above.

  本发明涉及具有抑制庚糖合成特性的新化合物，其具有式(I)或其药学上可接受的盐或前药，其中A为芳基或杂环，任选地被一个或多个相同或不同的R取代，如H、C1-C10烷基、C1-C10烷基-OR1、C1-C10烷基-NR1R1、烷氧基、羟基、硫代烷基、芳基、杂环、卤素、硝基、氰基、CO2R1、NR1R1、NR1C(O)R1、C(O)NR1R1、NR1C(S)R1、C(S)NR1R1、SO2NR1R1、SO2R1、NR1SO2R1、NR1C(O)NR1R1、NR1C(O)OR1、NR1C(S)NR1R1、NR1C(S)OR1、R1C═NOR1、C(O)R1、芳氧基、硫代芳基、烯基、炔基，R1相同或不同为H或C1-C10烷基；B1、B2、B3相同或不同，代表C、N、O、S以形成五元芳香环，其中一到三个碳原子被选自S、O、N的杂原子替换，任选地被一个或多个相同或不同的如上定义的R取代；B4为C或N；Y为H、C1-C10烷基、烷氧基、硫代烷基，任选地被一个或多个相同或不同的如上定义的R取代；W为C、O或N，被或不被一个或多个C1-C10烷基基团取代；D为任选地被一个或多个相同或不同的如上定义的R取代的杂环。
• Towards Gram-negative antivirulence drugs: New inhibitors of HldE kinase
  作者：Nicolas Desroy、François Moreau、Sophia Briet、Géraldine Le Fralliec、Stephanie Floquet、Lionel Durant、Vanida Vongsouthi、Vincent Gerusz、Alexis Denis、Sonia Escaich

  DOI：10.1016/j.bmc.2008.12.021

  日期：2009.2

  Gram-negative bacteria lacking heptoses in their lipopolysaccharide (LPS) display attenuated virulence and increased sensitivity to human serum and to some antibiotics. Thus inhibition of bacterial heptose synthesis represents an attractive target for the development of new antibacterial agents. HldE is a bifunctional enzyme involved in the synthesis of bacterial heptoses. Development of a biochemical assay suitable for high-throughput screening allowed the discovery of inhibitors 1 and 2 of HldE kinase. Study of the structure-activity relationship of this series of inhibitors led to highly potent compounds. (c) 2008 Elsevier Ltd. All rights reserved.